Maddinson on Friday beat out Cooper Connolly in the race to replace the injured Cameron Green, and has been listed to open alongside Travis Head in Durban.
That will leave Matt Renshaw batting at No.5, after opening in Australia's last Test against Bangladesh in Mackay in August.
Australia have now had three opening pairings in their past three Tests, following Jake Weatherald's axing after the loss to Bangladesh in Darwin.
Maddinson's call-up to the Test squad a week ago, after Josh Inglis fractured his finger, came as something of a shock.
The 34-year-old played three Tests in late 2016, but hasn't appeared for Australia in red-ball cricket since.
The left-hander only overcome a battle with testicular cancer last year, and has not played a first-class match since March 2025.
His call-up was initially met with some criticism given Maddinson's age, but Australia rate his ability to play spin.
There is also a thought there will be plenty of that on a Kingsmead wicket expected to become drier as the game goes on.
"We think he's really settled with where his game is at," Australia captain Pat Cummins said.
"He has shown good form."
South Africa are without spearhead quick Kagiso Rabada, who failed to overcome a hamstring injury.
The hosts picked two spinners, with Simon Harmer to partner Keshav Maharaj.
This series marks a clash between the world's top-two ranked sides, and Australia's first Tests in South Africa since the 2018 ball-tampering scandal.
"We would have liked to have batted first," South Africa captain Temba Bavuma said.
"It looks a nice wicket. Weather is good as well. We'll have to do the job with the ball."
AUSTRALIA: Travis Head, Nic Maddinson, Marnus Labuschagne, Steve Smith, Matt Renshaw, Alex Carey, Beau Webster, Mitchell Starc, Pat Cummins, Nathan Lyon, Josh Hazlewood
SOUTH AFRICA: Aiden Markram, Ryan Rickleton, David Bedingham, Temba Bavuma (capt), Tristan Stubbs, Wiaan Mulder, Kyle Verryenne, Marco Jansen, Keshav Maharaj, Simon Harmer, Andrich Nortje
